The present invention relates to the field of solid phase polymer synthesis. More specifically, the invention provides methods and derivatized supports which find application in solid phase synthesis of oligomer arrays or of single compounds on a preparative scale. The oligomer arrays which are prepared using the derivatized supports of the present invention may be used, for example, in screening studies for determination of binding affinity and in diagnostic applications.
The synthesis of biological polymers such as peptides and oligonucleotides has been evolving in dramatic fashion from the earliest stages of solution synthesis to solid phase synthesis of a single polymer to the more recent preparations of libraries having large numbers of diverse oligonucleotide sequences on a single solid support or chip.
Improved methods of forming large arrays of oligonucleotides, peptides and other polymer sequences in a short period of time have been devised. Of particular note, Pirrung et al., U.S. Pat. No. 5,143,854 (see also PCT Application No. WO 90/15070) and Fodor et al., PCT Publication No. WO 92/10092, all incorporated herein by reference, disclose methods of forming vast arrays of peptides, oligonucleotides and other polymer sequences using, for example, light-directed synthesis techniques. See also, Fodor et al, Science, 251:767-777 (1991), also incorporated herein by reference for all purposes. These procedures are now referred to as VLSIPS.TM. procedures.
In the above-referenced Fodor et al., PCT application, an elegant method is described for using a computer-controlled system to direct a VLSIPS.TM. procedure. Using this approach, one heterogenous array of polymers is converted, through simultaneous coupling at a number of reaction sites, into a different heterogenous array. See, Application Ser. Nos. 07/796,243 and 07/980,523, the disclosures of which are incorporated herein for all purposes.
The development of VLSIPS.TM. technology as described in the above-noted U.S. Pat. No. 5,143,854 and PCT patent publication Nos. WO 90/15070 and 92/10092, is considered pioneering technology in the fields of combinatorial synthesis and screening of combinatorial libraries. More recently, patent application Ser. No. 08/082,937, filed Jun. 25, 1993, describes methods for making arrays of oligonucleotide probes that can be used to provide a partial or complete sequence of a target nucleic acid and to detect the presence of a nucleic acid containing a specific oligonucleotide sequence.
The control of surface properties to optimize VLSIPS.TM. substrate performance in both chemical synthesis and bioassays has been recognized to involve such parameters as site density for synthesis initiation, surface wettability and the length of the linking group which attaches the initiation site to the surface. Additionally, alternative surfaces can lead to the use of VLSIPS.TM. technology for preparative scale synthesis.